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  • 1. Aqrawi, Lara A
    et al.
    Ivanchenko, Margarita
    Björk, Albin
    Ramírez Sepúlveda, Jorge I
    Imgenberg-Kreuz, Juliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kvarnström, Marika
    Haselmayer, Philipp
    Jensen, Janicke Liaaen
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chemin, Karine
    Skarstein, Kathrine
    Wahren-Herlenius, Marie
    Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing2018In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 192, no 3, p. 259-270Article in journal (Refereed)
    Abstract [en]

    cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS. This article is protected by copyright. All rights reserved.

  • 2.
    Björk, Albin
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
    Mofors, Johannes
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
    Kvarnström, Marika
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
    Forsblad-d'Elia, Helena
    Umea Univ, Dept Publ Hlth & Clin Med, Rheumatol, Umea, Sweden.
    Bucher, Sara Magnusson
    Orebro Univ, Dept Rheumatol, Fac Med & Hlth, Orebro, Sweden.
    Hillert, Jan
    Karolinska Inst, Karolinska Univ Hosp, Dept Clin Neurosci, Stockholm, Sweden.
    Eriksson, Per
    Linkoping Univ, Dept Clin Expt Med, Linkoping, Sweden.
    Mandl, Thomas
    Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Alfredsson, Lars
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Wahren-Herlenius, Marie
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
    Cigarette smoking is a risk factor for developing primary Sjögren's syndrome with Ro/SSA and La/SSB autoantibodies2018In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, no 3, p. S330-S330Article in journal (Other academic)
  • 3.
    Bolin, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gunnarsson, I.
    Sjowall, C.
    Eriksson, P.
    Forsblad-d'Elia, H.
    Jonsen, A.
    Theander, E.
    Omdal, R.
    Jonsson, R.
    Sivils, K.
    Wahren-Herlenius, M.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Early B Cell Factor 1 is Associated to Clinical Manifestations in Primary Sjogren's Syndrome and SLE2015In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 81, no 5, p. 416-416Article in journal (Other academic)
  • 4.
    Bolin, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Zickert, Agneta
    Jönsen, Andreas
    Sjöwall, Christopher
    Svenungsson, Elisabet
    Bengtsson, Anders A
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gunnarsson, Iva
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Association of STAT4 Polymorphism with Severe Renal Insufficiency in Lupus Nephritis2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. e84450-Article in journal (Refereed)
    Abstract [en]

    Lupus nephritis is a cause of significant morbidity in systemic lupus erythematosus (SLE) and its genetic background has not been completely clarified. The aim of this investigation was to analyze single nucleotide polymorphisms (SNPs) for association with lupus nephritis, its severe form proliferative nephritis and renal outcome, in two Swedish cohorts. Cohort I (n = 567 SLE cases, n = 512 controls) was previously genotyped for 5676 SNPs and cohort II (n = 145 SLE cases, n = 619 controls) was genotyped for SNPs in STAT4, IRF5, TNIP1 and BLK.

    Case-control and case-only association analyses for patients with lupus nephritis, proliferative nephritis and severe renal insufficiency were performed. In the case-control analysis of cohort I, four highly linked SNPs in STAT4 were associated with lupus nephritis with genome wide significance with p = 3.7×10−9, OR 2.20 for the best SNP rs11889341. Strong signals of association between IRF5 and an HLA-DR3 SNP marker were also detected in the lupus nephritis case versus healthy control analysis (p <0.0001). An additional six genes showed an association with lupus nephritis with p <0.001 (PMS2, TNIP1, CARD11, ITGAM, BLK and IRAK1). In the case-only meta-analysis of the two cohorts, the STAT4 SNP rs7582694 was associated with severe renal insufficiency with p = 1.6×10−3 and OR 2.22. We conclude that genetic variations in STAT4 predispose to lupus nephritis and a worse outcome with severe renal insufficiency.

  • 5. Bolstad, Anne Isine
    et al.
    Le Hellard, Stephanie
    Kristjansdottir, Gudlaug
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vasaitis, Lilian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Kvarnström, Marika
    Sjöwall, Christopher
    Johnsen, Svein Joar Auglænd
    Eriksson, Per
    Omdal, Roald
    Brun, Johan G
    Wahren-Herlenius, Marie
    Theander, Elke
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jonsson, Roland
    Association between genetic variants in the tumour necrosis factor/lymphotoxin α/lymphotoxin β locus and primary Sjogren's syndrome in Scandinavian samples2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, no 6, p. 981-988Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Lymphotoxin β (LTB) has been found to be upregulated in salivary glands of patients with primary Sjögren's syndrome (pSS). An animal model of pSS also showed ablation of the lymphoid organisation and a marked improvement in salivary gland function on blocking the LTB receptor pathway. This study aimed to investigate whether single-nucleotide polymorphisms (SNP) in the lymphotoxin α (LTA)/LTB/tumour necrosis factor (TNF) gene clusters are associated with pSS.

    METHODS:

    527 pSS patients and 532 controls participated in the study, all of Caucasian origin from Sweden and Norway. 14 SNP markers were genotyped and after quality control filtering, 12 SNP were analysed for their association with pSS using single marker and haplotype tests, and corrected by permutation testing.

    RESULTS:

    Nine markers showed significant association with pSS at the p=0.05 level. Markers rs1800629 and rs909253 showed the strongest genotype association (p=1.64E-11 and p=4.42E-08, respectively, after correcting for sex and country of origin). When the analysis was conditioned for the effect of rs1800629, only the association with rs909253 remained nominally significant (p=0.027). In haplotype analyses the strongest effect was observed for the haplotype rs909253G_rs1800629A (p=9.14E-17). The associations were mainly due to anti-Ro/SSA and anti-La/SSB antibody-positive pSS.

    CONCLUSIONS:

    A strong association was found between several SNP in the LTA/LTB/TNFα locus and pSS, some of which led to amino acid changes. These data suggest a role for this locus in the development of pSS. Further studies are needed to examine if the genetic effect described here is independent of the known genetic association between HLA and pSS.

  • 6. Brauner, Susanna
    et al.
    Kvarnstom, Marika
    Gorgen, Sabrina
    Franzen-Malmros, Michaela
    Brokstad, Karl A.
    Folkersen, Lasse
    Klareskog, Christina Trollmo Lars
    Jonsson, Roland
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Malmstrom, Vivianne
    Wahren-Herlenius, Marie
    Hyperreactive B Cells Upon Endosomal TLR Triggering Underlying Primary Sjogren's Syndrome2012In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 76, no 2, p. 199-200Article in journal (Other academic)
  • 7.
    Bremer, Hanna D.
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    Landegren, Nils
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Stockholm, Sweden..
    Sjöberg, Ronald
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, SE-17121 Solna, Sweden..
    Hallgren, Åsa
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, CMM, L8 01, SE-17176 Stockholm, Sweden..
    Renneker, Stefanie
    Euroimmun AG, D-23560 Lubeck, Germany..
    Lattwein, Erik
    Euroimmun AG, D-23560 Lubeck, Germany..
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, SE-17121 Solna, Sweden..
    Andersson, Goran
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Lilliehöök, Inger
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Broad Inst Harvard & MIT, Cambridge, USA..
    Kämpe, Olle
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, CMM, L8 01, SE-17176 Stockholm, Sweden.; Univ Bergen, Dept Clin Sci, N-5021 Bergen, Norway.;Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, N-5021 Bergen, Norway.;Haukeland Hosp, Dept Med, N-5021 Bergen, Norway..
    Hansson-Hamlin, Helene
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 4852Article in journal (Refereed)
    Abstract [en]

    Dogs can spontaneously develop complex systemic autoimmune disorders, with similarities to human autoimmune disease. Autoantibodies directed at self-antigens are a key feature of these autoimmune diseases. Here we report the identification of interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) as autoantigens in canine immune-mediated rheumatic disease. The ILF2 autoantibodies were discovered in a small, selected canine cohort through the use of human protein arrays; a method not previously described in dogs. Subsequently, ILF3 autoantibodies were also identified in the same cohort. The results were validated with an independent method in a larger cohort of dogs. ILF2 and ILF3 autoantibodies were found exclusively, and at a high frequency, in dogs that showed a speckled pattern of antinuclear antibodies on immunofluorescence. ILF2 and ILF3 autoantibodies were also found at low frequency in human patients with SLE and Sjogren's syndrome. These autoantibodies have the potential to be used as diagnostic biomarkers for canine, and possibly also human, autoimmune disease.

  • 8.
    Brito-Zeron, P.
    et al.
    Hosp CIMA Sanitas, Dept Med, Autoimmune Dis Unit, Barcelona, Spain;Univ Barcelona, Sjogrens Syndrome Res Grp AGAUR, Lab Autoimmune Dis Josep Font,Hosp Clin, IDIBAPS,CELLEX,Dept Autoimmune Dis,ICMiD, Barcelona, Spain.
    Acar-Denizli, N.
    Mimar Sinan Fine Arts Univ, Fac Sci & Letters, Dept Stat, Istanbul, Turkey.
    Ng, W. F.
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Zeher, M.
    Univ Debrecen, Fac Med, Div Clin Immunol, Debrecen, Hungary.
    Rasmussen, A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Mandl, T.
    Lund Univ, Skane Univ Hosp Malmo, Dept Rheumatol, Malmo, Sweden.
    Seror, R.
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, Ctr Immunol Viral Infect & Autoimmune Dis,INSERM, Paris, France.
    Li, X.
    Anhui Prov Hosp, Dept Rheumatol & Immunol, Hefei, Anhui, Peoples R China.
    Baldini, C.
    Univ Pisa, Rheumatol Unit, Pisa, Italy.
    Gottenberg, J. -E
    Danda, D.
    Christian Med Coll & Hosp, Dept Clin Immunol & Rheumatol, Vellore, Tamil Nadu, India.
    Quartuccio, L.
    Univ Hosp Santa Maria della Misericordia, Dept Med Area DAME, Clin Rheumatol, Udine, Italy.
    Priori, R.
    Sapienza Univ Rome, Rheumatol Clin, Dept Internal Med & Med Specialties, Rome, Italy.
    Hernandez-Molina, G.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Rheumatol & Immunol, Mexico City, DF, Mexico.
    Armagan, B.
    Hacettepe Univ, Fac Med, Dept Internal Med, Ankara, Turkey.
    Kruize, A. A.
    Univ Med Ctr Utrecht, Dept Rheumatol & Clin Immunol, Utrecht, Netherlands.
    Kwok, S. -K
    Kvarnstrom, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Praprotnik, S.
    Univ Med Ctr, Dept Rheumatol, Ljubljana, Slovenia.
    Sene, D.
    Paris Diderot Univ, Lariboisiere Hosp, AP HP, Dept Internal Med, Paris, France.
    Bartoloni, E.
    Univ Perugia, Dept Med, Rheumatol Unit, Perugia, Italy.
    Solans, R.
    Hosp Valle De Hebron, Dept Internal Med, Barcelona, Spain.
    Rischmueller, M.
    Univ Western Australia, Sch Med, Dept Rheumatol, Crawley, Australia.
    Suzuki, Y.
    Kanazawa Univ Hosp, Div Rheumatol, Kanazawa, Ishikawa, Japan.
    Isenberg, D. A.
    UCL, Div Med, Ctr Rheumatol, London, England.
    Valim, V.
    Univ Espirito Santo, Dept Med, Vitoria, Brazil;Univ Hosp HUCAM EBSERH, Vitoria, Brazil.
    Wiland, P.
    Wroclaw Med Hosp, Dept Rheumatol & Internal Med, Wroclaw, Poland.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Fraile, G.
    Hosp Ramon & Cajal, Dept Internal Med, Madrid, Spain.
    Bootsma, H.
    Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, Groningen, Netherlands.
    Nakamura, T.
    Nagasaki Univ, Grad Sch Biomed Sci, Dept Radiol & Canc Biol, Nagasaki, Japan.
    Giacomelli, R.
    Univ Aquila, Sch Med, Clin Unit Rheumatol, Laquila, Italy.
    Devauchelle-Pensec, V.
    Brest Univ Hosp, Dept Rheumatol, Brest, France.
    Knopf, A.
    Tech Univ Munich, Klinikum Rechts Isar, Otorhinolaryngol Head & Neck Surg, Munich, Germany.
    Bombardieri, M.
    Queen Mary Univ London, Ctr Expt Med & Rheumatol, London, England.
    Trevisani, V. -F
    Univ Fed Sao Paulo, Sao Paulo, Brazil.
    Hammenfors, D.
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Rheumatol, Bergen, Norway.
    Pasoto, S. G.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Rheumatol, Sao Paulo, Brazil.
    Retamozo, S.
    Univ Nacl Cordoba, Consejo Nacl Invest Cient & Tecn CONICET, Inst Invest Ciencias Salud INICSA, Hosp Privado Univ Cordoba,IUCBC, Cordoba, Argentina.
    Gheita, T. A.
    Cairo Univ, Kasr Al Ainy Sch Med, Dept Rheumatol, Cairo, Egypt.
    Atzeni, F.
    IRCCS Galeazzi Orthopaed Inst, Milan, Italy;Univ Messina, Rheumatol Unit, Messina, Italy.
    Morel, J.
    Montpellier Univ Hosp, Dept Rheumatol, Montpellier, France;Univ Montpellier, Montpellier, France.
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina.
    Horvath, I-F
    Sivils, K. L.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Olsson, P.
    Lund Univ, Skane Univ Hosp Malmo, Dept Rheumatol, Malmo, Sweden.
    De Vita, S.
    Univ Hosp Santa Maria della Misericordia, Dept Med Area DAME, Clin Rheumatol, Udine, Italy.
    Sanchez-Guerrero, J.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Rheumatol & Immunol, Mexico City, DF, Mexico.
    Kilic, L.
    Hacettepe Univ, Fac Med, Dept Internal Med, Ankara, Turkey.
    Wahren-Herlenius, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Mariette, X.
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, Ctr Immunol Viral Infect & Autoimmune Dis,INSERM, Paris, France.
    Ramos-Casals, M.
    Univ Barcelona, Sjogrens Syndrome Res Grp AGAUR, Lab Autoimmune Dis Josep Font,Hosp Clin, IDIBAPS,CELLEX,Dept Autoimmune Dis,ICMiD, Barcelona, Spain.
    How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project)2018In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, no 3, p. S102-S112Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjogren's syndrome (SjS).

    Methods: The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.

    Results: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti-La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglobulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for ctyoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESSDAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).

    Conclusion: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.

  • 9.
    Brito-Zeron, P.
    et al.
    Hosp CIMA Sanitas, Barcelona, Spain.;Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey..
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J-E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A. A.
    UMC, Utrecht, Netherlands..
    Park, S-H
    Kvarnstrom, M.
    Karolinska Inst, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Alunno, A.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hosp Valle De Hebron, Barcelona, Spain..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Suzuki, Y.
    Univ Kanazawa, Kanazawa, Ishikawa, Japan..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Wiland, P.
    Med Hosp, Wroclaw, Poland..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    UFES, Vitoria, Spain..
    Giacomelli, R.
    Univ Aquila, Laquila, Italy..
    Seror, R.
    Univ Sud, Paris, France..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombardieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Minniti, A.
    Sapienza Univ, Rome, Italy..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjögren Syndrome: Characterization Of Systemic Disease2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 464-465Article in journal (Other academic)
  • 10.
    Brito-Zeron, P.
    et al.
    Hosp CIMA Sanitas, Barcelona, Spain.;Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey..
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J-E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A. A.
    UMC, Utrecht, Netherlands..
    Park, S-H
    Kvarnstrom, M.
    Karolinska Instit, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hasp Vall Hebron, Barcelona, Spain..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Suzuki, Y.
    Univ Kanazawa, Kanazawa, Ishikawa, Japan..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Sebastian, A.
    Med Hosp, Wroclaw, Poland..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    Univ Fed Espirito Santo, Vitoria, Brazil..
    Giacomelli, R.
    Univ Nagasaki, Nagasaki, Japan.;Univ Aquila, Laquila, Italy..
    Seror, R.
    Univ Paris Sud, Paris, France..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombaidieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ Hasp, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Paris Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Predicting Survival In 6240 Patients With Primary Sjögren' Syndrome (Big Data Sjögren Project)2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 311-311Article in journal (Other academic)
  • 11.
    Brito-Zeron, P.
    et al.
    Hosp Clínic, Barcelona, Spain.
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey.
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Univ Paris Sud, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMC, Utrecht, Netherlands..
    Park, S. -H
    Catholic Univ Korea, Seoul, South Korea..
    Kvarnstrom, M.
    Karolinska Inst, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hosp Valle De Hebron, Barcelona, Spain..
    Suzuki, Y.
    Univ Hosp, Kanazawa, Ishikawa, Japan..
    Isenberg, D.
    UCL, London, England..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Sebastian, A.
    Med Hosp, Wroclaw, Poland..
    Vissink, A.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    Univ Fed Espirito Santo, Vitoria, Brazil..
    Giacomelli, R.
    Univ Aquila, Laquila, Italy..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombardieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Carsons, S. E.
    Sch Med SBU, Mineola, NY USA..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Paris Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Analysis Of 9302 Patients From The Big Data International Primary Sjogren Syndrome Cohort: Clinical Presentation At Diagnosis Of European Vs Non-European Patients2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 886-887Article in journal (Other academic)
  • 12.
    Brito-Zeron, P.
    et al.
    Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Mimar Sinan Univ, Istanbul, Turkey..
    Zeher, M.
    Debrecen Univ, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Paris Sud Univ, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Peoples R China..
    Baldini, C.
    Rheumatol Clin, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Hernandez-Molina, G.
    INNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMCU, Utrecht, Netherlands..
    Valim, V.
    Espirito Santo Univ, Vitoria, Spain..
    Kvarnstrom, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Perugia Univ, Perugia, Italy..
    Praprotnik, S.
    Clin Ctr Univ, Ljubljana, Slovenia..
    Isenberg, D.
    UCL, London, England..
    Solans, R.
    Vall Hebron Hosp, Barcelona, Spain..
    Rischmueller, M.
    Queen Elizabeth Hosp, Woodville, SA, Australia..
    Kwok, S. -K
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Suzuki, Y.
    Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Giacomelli, R.
    Laquila Univ, Laquila, Italy..
    Devauchelle-Pensec, V.
    Brest Univ Hosp, Brest, France..
    Bombardieri, M.
    QMUL, London, England..
    Hofauer, B.
    Rechts Isar Hosp, Munich, Germany..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands.;Haukeland Hosp, Bergen, Norway..
    Hammenfors, D.
    Fraile, G.
    Ramon Cajal Hosp, Madrid, Spain..
    Carsons, S.
    SUNY Stony Brook, Mineola, NY USA..
    Gheita, T.
    Cairo Univ, Cairo, Egypt..
    Morel, J.
    Montpellier Hosp, Montpellier, France..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Retamozo, S.
    Privado Hosp, Cordoba, Argentina..
    Horvath, I. -F
    Sivils, K.
    OMRF, Oklahoma City, OK USA..
    Theander, E.
    Lund Univ, Malmo, Sweden..
    Sandhya, P.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    De Vita, S.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Sanchez-Guerrero, J.
    INNSZ, Mexico City, DF, Mexico..
    van der Heijden, E.
    UMCU, Utrecht, Netherlands..
    Moca-Trevisano, V.
    Sao Paulo Fed Univ, Sao Paulo, Brazil..
    Wahren-Herlenius, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Mariette, X.
    Paris Sud Univ, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Worldwide Heterogeneous Diagnostic Approach To Primary Sjögren Syndrome in 8315 Patients (EULAR-SS Task Force Big Data Sjögren Project)2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. 314-315Article in journal (Other academic)
  • 13.
    Brito-Zeron, P.
    et al.
    Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Mimar Sinan Univ, Istanbul, Turkey..
    Zeher, M.
    Debrecen Univ, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Paris Sud Univ, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Peoples R China..
    Baldini, C.
    Rheumatol Clin, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Hernandez-Molina, G.
    INNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMCU, Utrecht, Netherlands..
    Valim, V.
    Espirito Santo Univ, Vitoria, Brazil..
    Kvarnstrom, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Gerli, R.
    Perugia Univ, Perugia, Italy..
    Praprotnik, S.
    Clin Ctr Univ, Ljubljana, Slovenia..
    Isenberg, D.
    UCL, London, England..
    Solans, R.
    Vall Hebron Hosp, Barcelona, Spain..
    Rischmueller, M.
    Queen Elizabeth Hosp, Woodville, SA, Australia..
    Park, S. -H
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Suzuki, Y.
    Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Giacomelli, R.
    LAquila Univ, Laquila, Italy..
    Saraux, A.
    Brest Univ Hosp, Brest, France..
    Bombardieri, M.
    QMUL, London, England..
    Hofauer, B.
    Rechts Isar Hosp, Munich, Germany..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Fraile, G.
    Ramon Cajal Hosp, Madrid, Spain..
    Carsons, S.
    SUNY Stony Brook, Mineola, NY USA..
    Gheita, T.
    Cairo Univ, Cairo, Egypt..
    Morel, J.
    Montpellier Hosp, Montpellier, France..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Retamozo, S.
    Privado Hosp, Cordoba, Argentina..
    Horvath, I. -F
    Sivils, K.
    OMRF, Oklahoma City, OK USA..
    Theander, E.
    Lund Univ, Malmo, Sweden..
    Sandhya, P.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    De Vita, S.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Sanchez-Guerrero, J.
    INNSZ, Mexico City, DF, Mexico..
    van der Heijden, E.
    UMCU, Utrecht, Netherlands..
    Moca-Trevisano, V.
    Sao Paulo Fed Univ, Sao Paulo, Brazil..
    Wahren-Herlenius, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Mariette, X.
    Paris Sud Univ, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Ethnic Differences Strongly Influence The Phenotypic Expression of Primary Sjögren: Study of 7887 Patients from 20 Countries on 5 Continents (EULAR-SS Task Force Big Data Sjögren Project)2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. 772-772Article in journal (Other academic)
  • 14.
    Brito-Zeron, Pilar
    et al.
    Hosp Clin Barcelona, CELLEX IDIBAPS, Dept Autoimmune Dis, Barcelona, Spain..
    Retamozo, Soledad
    Hosp Clin Barcelona, CELLEX IDIBAPS, Dept Autoimmune Dis, Barcelona, Spain.;Hosp Privado Ctr Med Cordoba, Rheumatol Unit, Cordoba, Argentina..
    Zeher, Margit
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, Astrid
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Theander, Elke
    Lund Univ, Skane Univ Hosp Malmo, Malmo, Sweden..
    Gottenberg, Jacques
    Hop Univ Strasbourg, Strasbourg, France..
    Baldini, Chiara
    Univ Pisa, Rheumatol Unit, Pisa, Italy..
    Quartuccio, Luca
    Univ Udine, Santa Maria Misericordia Hosp, Clin Rheumatol, Dept Med & Biol Sci DSMB, I-33100 Udine, Italy..
    Priori, Roberta
    Univ Roma La Sapienza, Rheumatol Unit, I-00185 Rome, Italy..
    Valim, Valeria
    Univ Fed Espirito Santo, Rheumatol, Vitoria, Brazil..
    Kvarnstrom, Marika
    Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Kruize, Aike
    Univ Med Ctr Utrecht, Rheumatol & Clin Immunol, Utrecht, Netherlands..
    Hernandez-Molina, Gabriela
    Inst Nacl Ciencias Med Nutr Salvador Zubiran, Immunol & Rheumatol, Mexico City, DF, Mexico..
    Bartoloni-Bocci, Elena
    Univ Perugia, Rheumatol Unit, Dept Med, I-06100 Perugia, Italy..
    Praprotnik, Sonja
    Univ Med Ctr Ljubljana, Dept Rheumatol, Ljubljana, Slovenia..
    Isenberg, David A.
    UCL Div Med, Ctr Rheumatol Res, Rayne Inst, London, England..
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Bombardieri, Michele
    Queen Mary Univ London, Expt Med & Rheumatol, London, England..
    Suzuki, Yasunori
    Kanazawa Univ, Grad Sch Med, Kanazawa, Ishikawa, Japan..
    Solans, Roser
    Hosp Valle De Hebron, Dept Internal Med, Barcelona, Spain..
    Giacomelli, Roberto
    Univ Aquila, I-67100 Laquila, Italy..
    Hammenfors, Daniel S.
    Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway..
    Carsons, Steven E.
    Winthrop Univ Hosp, Rheumatol Allergy & Immunol, Mineola, NY 11501 USA..
    Boostma, Hendrika
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands..
    Vollenweider, Cristina F.
    German Hosp, Rheumatol, Buenos Aires, DF, Argentina..
    Atzeni, Fabiola
    L Sacco Univ Hosp Milan, Rheumatol Unit, Milan, Italy..
    Sivils, Kathy
    Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA..
    Mandl, Thomas
    Lund Univ, Dept Rheumatol, Skane Univ Hosp Malmo, Malmo, Sweden..
    De Vita, Salvatore
    Univ Udine, Santa Maria Misericordia Hosp, I-33100 Udine, Italy..
    Wahren-Herlenius, Marie
    Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Kawano, Mitsuhiro
    Kanazawa Univ, Div Rheumatol, Grad Sch Med, Kanazawa, Ishikawa, Japan..
    Gerli, Roberto
    Univ Perugia, I-06100 Perugia, Italy..
    Vissink, Arjan
    Univ Groningen, Univ Med Ctr Groningen, Dept Oral & Maxillofacial Surg, Groningen, Netherlands..
    Brun, Johan G.
    Haukeland Hosp, N-5021 Bergen, Norway..
    Trevisani, Virginia
    Univ Fed Sao Paulo, Hlth Evidence Based, Sao Paulo, Brazil..
    Sanchez-Guerrero, Jorge
    Mt Sinai Hosp, Rheumatol, Toronto, ON M5G 1X5, Canada.;Univ Hlth Network, Toronto, ON M5G 1X5, Canada..
    Mariette, Xavier
    Univ Paris 11, Hop Univ Paris Sud, AP HP, Paris, France..
    Ramos-Casals, Manuel
    Hosp Clin Barcelona, CELLEX IDIBAPS, Dept Autoimmune Dis, Barcelona, Spain..
    Big Data International Primary Sjogren Syndrome Registry: Baseline Characterization and Diagnostic Approach in 6047 Patients Fulfilling the 2002 AE Criteria2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl. 10, article id 634Article in journal (Other academic)
  • 15. Brito-Zerón, Pilar
    et al.
    Acar-Denizli, Nihan
    Zeher, Margit
    Rasmussen, Astrid
    Seror, Raphaele
    Theander, Elke
    Li, Xiaomei
    Baldini, Chiara
    Gottenberg, Jacques-Eric
    Danda, Debashish
    Quartuccio, Luca
    Priori, Roberta
    Hernandez-Molina, Gabriela
    Kruize, Aike A
    Valim, Valeria
    Kvarnstrom, Marika
    Sene, Damien
    Gerli, Roberto
    Praprotnik, Sonja
    Isenberg, David
    Solans, Roser
    Rischmueller, Maureen
    Kwok, Seung-Ki
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Suzuki, Yasunori
    Giacomelli, Roberto
    Devauchelle-Pensec, Valerie
    Bombardieri, Michele
    Hofauer, Benedikt
    Bootsma, Hendrika
    Brun, Johan G
    Fraile, Guadalupe
    Carsons, Steven E
    Gheita, Tamer A
    Morel, Jacques
    Vollenveider, Cristina
    Atzeni, Fabiola
    Retamozo, Soledad
    Horvath, Ildiko Fanny
    Sivils, Kathy
    Mandl, Thomas
    Sandhya, Pulukool
    De Vita, Salvatore
    Sanchez-Guerrero, Jorge
    van der Heijden, Eefje
    Trevisani, Virginia Fernandes Moça
    Wahren-Herlenius, Marie
    Mariette, Xavier
    Ramos-Casals, Manuel
    Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, no 6, p. 1042-1050Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis.

    METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed.

    RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69).

    CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.

  • 16.
    Båve, Ullvi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lövgren, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cajander, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eloranta, Maija-Leena
    Alm, Gunnar V.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Activation of the type I interferon system in primary Sjögren's syndrome: a possible etiopathogenic mechanism2005In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 52, no 4, p. 1185-1195Article in journal (Refereed)
    Abstract [en]

    Objective

    The etiopathogenesis of primary Sjögren's syndrome (SS) is largely unknown. In other autoimmune diseases, type I interferon (IFN) may play a pivotal role by triggering and sustaining the disease process. We therefore aimed to determine whether patients with primary SS had an activated type I IFN system.

    Methods

    Salivary gland biopsy specimens and sera from patients with primary SS were investigated for the occurrence of IFNα-producing cells and measurable IFNα levels, respectively. The ability of primary SS sera together with apoptotic or necrotic cells to induce IFNα production in normal peripheral blood mononuclear cells was examined. The IFNα inducer was characterized, and IFNα-producing cells were identified. Clinical data were correlated with the IFNα-inducing capacity of primary SS sera.

    Results

    Numerous IFNα-producing cells were detected in salivary gland biopsy specimens, despite low serum IFNα levels. Autoantibodies to RNA-binding proteins, combined with material released by necrotic or late apoptotic cells, were potent inducers of IFNα production in plasmacytoid dendritic cells (PDCs). This appeared to be attributable to RNA-containing immune complexes triggering PDCs by means of RNA and interaction with Fcγ receptor IIa. The IFNα-inducing capacity of sera was associated with positive results of a labial salivary gland biopsy (focus score ≥1) and with dermatologic, hematologic, and pulmonary manifestations.

    Conclusion

    Patients with primary SS have an activated type I IFN system. Although virus may initiate the production of IFN, the continued IFNα synthesis is caused by RNA-containing immune complexes that activate PDCs to prolong IFNα production at the tissue level. This IFNα promotes the autoimmune process by a vicious circle–like mechanism, with increased autoantibody production and formation of more endogenous IFNα inducers.

  • 17.
    Carlsson Almlöf, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Sylwan, Lina
    Karolinska Inst, Dept Biosci & Nutr, Sci Life Lab SciLifeLab, Solna, Sweden..
    Bäcklin, Christofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tandre, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Bengtsson, Christine
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Jonsen, Andreas
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Dahlqvist, Solbritt Rantapaa
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Sjowall, Christopher
    Linkoping Univ, Dept Clin & Expt Med, AIR Rheumatol, Linkoping, Sweden..
    Bengtsson, Anders A.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Novel risk genes for systemic lupus erythematosus predicted by random forest classification2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 6236Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.

  • 18.
    Eriksson, Karin G.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zickert, Agneta
    Sandling, Johanna K.
    Jonsen, Andreas
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Behrens, Timothy W.
    Graham, Robert R.
    Ortmann, Ward
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Gunnarsson, Iva
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Association of STAT4, IRF5 and BLK polymorphisms with severity and outcome in lupus nephritis2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, p. A55-A55Article in journal (Other academic)
  • 19. Feng, Di
    et al.
    Stone, Rivka C.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sangster-Guity, Niquiche
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sigurdsson, Snaevar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wang, Chuan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alm, Gunnar
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barnes, Betsy J.
    Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus2010In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, no 2, p. 562-573Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Genetic variants of the interferon (IFN) regulatory factor 5 gene (IRF5) are associated with susceptibility to systemic lupus erythematosus (SLE). The contribution of these variants to IRF-5 expression in primary blood cells of SLE patients has not been addressed, nor has the role of type I IFNs. The aim of this study was to determine the association between increased IRF-5 expression and the IRF5 risk haplotype in SLE patients. METHODS: IRF-5 transcript and protein levels in 44 Swedish patients with SLE and 16 healthy controls were measured by quantitative real-time polymerase chain reaction, minigene assay, and flow cytometry. Single-nucleotide polymorphisms rs2004640, rs10954213, and rs10488631 and the CGGGG insertion/deletion were genotyped in these patients. Genotypes of these polymorphisms defined both a common risk haplotype and a common protective haplotype. RESULTS: IRF-5 expression and alternative splicing were significantly up-regulated in SLE patients compared with healthy donors. Enhanced transcript and protein levels were associated with the risk haplotype of IRF5; rs10488631 displayed the only significant independent association that correlated with increased transcription from the noncoding first exon 1C. Minigene experiments demonstrated an important role for rs2004640 and the CGGGG insertion/deletion, along with type I IFNs, in regulating IRF5 expression. CONCLUSION: This study provides the first formal proof that IRF-5 expression and alternative splicing are significantly up-regulated in primary blood cells of patients with SLE. Furthermore, the risk haplotype is associated with enhanced IRF-5 transcript and protein expression in patients with SLE.

  • 20.
    Gallo, Lina Marcela Diaz
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Lundstrom, Emeli
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Oke, Vilija
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Elvin, Kerstin
    Karolinska Univ Hosp, Karolinska Inst, Dept Clin Immunol & Transfus Med, Unit Clin Immunol,Dept Med Solna,Rheumatol Unit, Stockholm, Sweden..
    Wu, Yee Ling
    Nationwide Childrens Hosp, Res Inst, Columbus, OH USA.;Ohio State Univ, Columbus, OH 43210 USA..
    Gustafsson, Johanna
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Jonsen, Andreas
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zickert, Agneta
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Bengtsson, Anders A.
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Yu, Chack-Yung
    Nationwide Childrens Hosp, Res Inst, Ctr Mol & Human Genet, Columbus, OH USA..
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    SLE Comprises Four Immune-Phenotypes, Which Differ Regarding HLA-DRB1 and Clinical Associations2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no S10, article id 1675Article in journal (Other academic)
  • 21. Gateva, Vesela
    et al.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Hom, Geoff
    Taylor, Kimberly E.
    Chung, Sharon A.
    Sun, Xin
    Ortmann, Ward
    Kosoy, Roman
    Ferreira, Ricardo C.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Padyukov, Leonid
    Sturfelt, Gunnar
    Jönsen, Andreas
    Bengtsson, Anders A.
    Rantapää-Dahlqvist, Solbritt
    Baechler, Emily C.
    Brown, Elizabeth E.
    Alarcón, Graciela S.
    Edberg, Jeffrey C.
    Ramsey-Goldman, Rosalind
    McGwin, Gerald
    Reveille, John D.
    Vilá, Luis M.
    Kimberly, Robert P.
    Manzi, Susan
    Petri, Michelle A.
    Lee, Annette
    Gregersen, Peter K.
    Seldin, Michael F.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Criswell, Lindsey A.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Behrens, Timothy W.
    Graham, Robert R.
    A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus2009In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 41, no 11, p. 1228-1233Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.

  • 22. Haldorsen, K
    et al.
    Appel, S
    Le Hellard, S
    Bruland, O
    Brun, J G
    Omdal, R
    Kristjansdottir, Gudlaug
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Theander, E
    Fernandes, C P D
    Kvarnström, M
    Eriksson, P
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Herlenius, M W
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Jonsson, R
    Bolstad, A I
    No association of primary Sjogren's syndrome with Fc gamma receptor gene variants2013In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 14, no 4, p. 234-237Article in journal (Refereed)
    Abstract [en]

    The genetic background of primary Sjögren's syndrome (pSS) is partly shared with systemic lupus erythematosus (SLE). Immunoglobulin G Fc receptors are important for clearance of immune complexes. Fcγ receptor variants and gene deletion have been found to confer SLE risk. In this study, four Fcγ receptor single-nucleotide polymorphisms (SNPs) and one copy number variation (CNV) were studied. Swedish and Norwegian pSS patients (N=527) and controls (N=528) were genotyped for the Fcγ receptor gene variant FCGR2A H131R (rs1801274) by the Illumina GoldenGate assay. FCGR3A F158V (rs396991) was analysed in 488 patients and 485 controls, FCGR3B rs447536 was analysed in 471 patients and 467 controls, and FCGR3B rs448740 was analysed in 478 cases and 455 controls, using TaqMan SNP genotyping assays. FCGR3B CNV was analysed in 124 patients and 139 controls using a TaqMan copy number assay. None of the SNPs showed any association with pSS. Also, no FCGR3B CNV association was detected. The lack of association of pSS with Fcγ receptor gene variants indicates that defective immune complex clearance may not be as important in pSS pathogenesis as in SLE, and may point to important differences between SLE and pSS.

  • 23. Haldorsen, Karstein
    et al.
    Appel, Silke
    Le Hellard, Stephanie
    Bruland, Ove
    Brun, Johan G.
    Omdal, Roald
    Kristjansdottir, Gudlaug
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Theander, Elke
    Fernandes, Carla P. D.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Kvarnstrom, Marika
    Eriksson, Per
    Ronnblom, Lars
    Herlenius, Marie Wahren
    Jonsson, Roland
    Bolstad, Anne Isine
    No Association of Primary Sjogren's Syndrome with Fcγ?Receptor Gene Variants2012In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 76, no 2, p. 198-198Article in journal (Other academic)
  • 24.
    Harris, Valerie M.
    et al.
    Univ Oklahoma, Hlth Sci Ctr, Pathol, Oklahoma City, OK USA..
    Cavett, Joshua
    Univ Oklahoma, Hlth Sci Ctr, Med, Oklahoma City, OK USA..
    Kurien, Biji
    Oklahoma Med Res Fdn, Arthrit & Immunol, Oklahoma City, OK 73104 USA..
    Liu, Ke
    Univ Cincinnati & Cincinnati Childre, Cincinnati, OH USA..
    Koelsch, Kristi A.
    Oklahoma Med Res Fdn, Arthrit& Clin Immunol, Okalahoma City, OK USA..
    Radfar, Lida
    Univ Oklahoma, Hlth Sci Ctr, Coll Dent, Oral Diag & Radiol Dept, Oklahoma City, OK USA..
    Lewis, David M.
    Univ Oklahoma, Hlth Sci Ctr, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA..
    Stone, Donald U.
    King Khalid Eye Specialist Hosp, Riyadh, Saudi Arabia..
    Li, Shibo
    Univ Oklahoma, Hlth Sci Ctr, Pediat, Oklahoma City, OK USA..
    Segal, Barbara
    Univ Minnesota, Rheumatol, Minneapolis, MN USA..
    Wallace, Daniel J.
    Cedars Sinai Med Ctr, West Hollywood, CA USA..
    Weisman, Michael H.
    Cedars Sinai Med Ctr, Rheumatol, Los Angeles, CA 90048 USA..
    Kelly, Jennifer A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Alarcon-Riquelme, Marta
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, Oklahoma City, OK USA..
    Pons-Estel, Bernado
    Hosp Prov Rosario, Rosario, Santa Fe, Argentina..
    Jonsson, Roland
    Broegelmann Res Lab, Bergen, Norway..
    Lu, Xianglan
    Univ Oklahoma, Hlth Sci Ctr, Pediat, Oklahoma City, OK USA..
    Gottenberg, Jacques
    Hautepierre, Strasbourg, France..
    Anaya, Juan-Manuel
    CIB Rosario Univ, Cell Biol & Immunogenet, Medellin, Colombia..
    Cunninghame-Graham, Deborah S.
    Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England..
    Keystone, Edward C.
    Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada..
    Huang, Andrew J. W.
    Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA..
    Brennan, Michael T.
    Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA..
    Hughes, Pamela
    Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA..
    Illei, G.
    NIDCR, Sjogrens Clin, NIH, Bethesda, MD USA..
    Miceli, Corinne
    Bykerk, V. P.
    Univ Toronto, Toronto, ON, Canada..
    Hirschfield, Gideon
    Univ Birmingham, Coll Med & Dent Sci, Inst Biomed Res, Ctr Liver Res,Sch Immun & Infect, Birmingham, W Midlands, England..
    Xie, Gang
    Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada..
    Ng, Wan-Fai
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England..
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eriksson, Per
    Linkoping Univ Hosp, Rheumatol Clin, S-58185 Linkoping, Sweden..
    Omdal, Roald
    Clin Immunol Unit, Dept Internal Med, Stavanger, Norway..
    Rhodus, Nelson L.
    Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA..
    Rischmueller, Maureen
    Queen Elizabeth Hosp, Rheumatol, Adelaide, SA, Australia..
    Rohrer, Michael D.
    Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA..
    Wahren-Herlenius, Marie
    Expt Rheumatol Unit, Dept Med, Solna, Sweden..
    Witte, Torsten
    Hannover Med Sch, Dept Immunol & Rheumatol, Hannover, Germany..
    Mariette, Xavier
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, Paris, France..
    Lessard, Christopher
    Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA..
    Harley, John B.
    Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA..
    Sivils, Kathy L.
    Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA..
    Scofield, Robert Hal
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.;US Dept Vet Affairs Med Ctr, Oklahoma City, OK USA..
    Klinefelter's Syndrome (47,XXY) Among Men with Sjogren's Syndrome2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl. 10, article id 648Article in journal (Other academic)
  • 25. Harris, Valerie M.
    et al.
    Sharma, Rohan
    Cavett, Joshua
    Kurien, Biji T
    Liu, Ke
    Koelsch, Kristi A
    Rasmussen, Astrid
    Radfar, Lida
    Lewis, David
    Stone, Donald U
    Kaufman, C Erick
    Li, Shibo
    Segal, Barbara
    Wallace, Daniel J
    Weisman, Michael H
    Venuturupalli, Swamy
    Kelly, Jennifer A
    Alarcon-Riquelme, Marta E
    Pons-Estel, Bernardo
    Jonsson, Roland
    Lu, Xianglan
    Gottenberg, Jacques-Eric
    Anaya, Juan-Manuel
    Cunninghame-Graham, Deborah S
    Huang, Andrew J W
    Brennan, Michael T
    Hughes, Pamela
    Alevizos, Ilias
    Miceli-Richard, Corinne
    Keystone, Edward C
    Bykerk, Vivian P
    Hirschfield, Gideon
    Xie, Gang
    Ng, Wan-Fai
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bucher, Sara Magnusson
    Eriksson, Per
    Omdal, Roald
    Rhodus, Nelson L
    Rischmueller, Maureen
    Rohrer, Michael
    Wahren-Herlenius, Marie
    Witte, Torsten
    Mariette, Xavier
    Lessard, Christopher J
    Harley, John B
    Sivils, Kathy L
    Scofield, R Hal
    Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome2016In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 168, p. 25-29Article in journal (Refereed)
    Abstract [en]

    Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fisher's exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p=NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA.

  • 26.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Umeå, Sweden.
    Bengtsson, Anders A
    Lund University, Skane University Hospital, Lund, Sweden.
    Jönsen, Andreas
    Lund University, Skane University Hospital, Lund, Sweden.
    Padyukov, Leonid
    Karolinska University Hospital, Stockholm, Sweden.
    Gunnarsson, Iva
    Karolinska University Hospital, Stockholm, Sweden.
    Svenungsson, Elisabet
    Karolinska University Hospital, Stockholm, Sweden.
    Sjöwall, Christopher
    Linköping University, Linköping, Sweden.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 5, p. 736-743Article in journal (Refereed)
    Abstract [en]

    Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with heterogeneous presentation and complex aetiology where DNA methylation changes are emerging as a contributing factor. In order to discover novel epigenetic associations and investigate their relationship to genetic risk for SLE, we analysed DNA methylation profiles in a large collection of patients with SLE and healthy individuals.

    Methods: DNA extracted from blood from 548 patients with SLE and 587 healthy controls were analysed on the Illumina HumanMethylation 450 k BeadChip, which targets 485 000 CpG sites across the genome. Single nucleotide polymorphism (SNP) genotype data for 196 524 SNPs on the Illumina ImmunoChip from the same individuals were utilised for methylation quantitative trait loci (cis-meQTLs) analyses.

    Results: We identified and replicated differentially methylated CpGs (DMCs) in SLE at 7245 CpG sites in the genome. The largest methylation differences were observed at type I interferon-regulated genes which exhibited decreased methylation in SLE. We mapped cis-meQTLs and identified genetic regulation of methylation levels at 466 of the DMCs in SLE. The meQTLs for DMCs in SLE were enriched for genetic association to SLE, and included seven SLE genome-wide association study (GWAS) loci: PTPRC (CD45), MHC-class III, UHRF1BP1, IRF5, IRF7, IKZF3 and UBE2L3. In addition, we observed association between genotype and variance of methylation at 20 DMCs in SLE, including at the HLA-DQB2 locus.

    Conclusions: Our results suggest that several of the genetic risk variants for SLE may exert their influence on the phenotype through alteration of DNA methylation levels at regulatory regions of target genes.

  • 27.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Sjowall, Christopher
    Linkoping Univ, Rheumatol AIR, Dept Clin & Expt Med, Linkoping, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Treatment-Associated DNA Methylation Patterns in Systemic Lupus Erythematosus2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no S10, article id 2654Article in journal (Other academic)
  • 28.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rantapaa-Dahlqvist, S.
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden.
    Bengtsson, A.
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden.
    Jonsen, A.
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden.
    Padyukov, L.
    Karolinska Inst, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden.
    Gunnarsson, I.
    Karolinska Inst, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden.
    Svenungsson, E.
    Karolinska Inst, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden.
    Sjowall, C.
    Linkoping Univ, Rheumatol Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Shared and unique patterns of DNA methylation in primary Sjogren's syndrome and systemic lupus erythematosus2018In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 3-3Article in journal (Other academic)
  • 29.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Signer, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Norheim, Katrine B.
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Eloranta, Majia-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvanen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hypomethylation in Enhancer and Promoter Regions of Interferon Regulated Genes in Multiple Tissues Is Associated with Primary Sjogren's Syndrome2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl. 10, article id 2100Article in journal (Other academic)
  • 30.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Signér, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Norheim, Katrine Braekke
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, no 11, p. 2029-2036Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjögren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls.

    METHODS: Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed.

    RESULTS: We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed.

    CONCLUSIONS: Our study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology.

  • 31.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sandling, Johanna K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Bjork, A.
    Karolinska Inst, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden.
    Nordlund, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kvarnstrom, M.
    Karolinska Inst, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wahren-Herlenius, M.
    Karolinska Inst, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Transcription profiling of peripheral B cells in antibody-positive primary Sjogren's syndrome reveals upregulated expression of CX3CR1 and a type I and type II interferon signature2018In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 87, no 5, article id UNSP e12662Article in journal (Refereed)
    Abstract [en]

    B cells play a key role in the pathogenesis of primary Sjogren's syndrome (pSS). The aim of this study was to analyse the transcriptome of CD19+ B cells from patients with pSS and healthy controls to decipher the B cell-specific contribution to pSS. RNA from purified CD19+ B cells from 12 anti-SSA antibody-positive untreated female patients with pSS and 20 healthy blood donors was subjected to whole transcriptome sequencing. A false discovery rate corrected significance threshold of <0.05 was applied to define differential gene expression. As validation, gene expression in B cells from 17 patients with pSS and 16 healthy controls was analysed using a targeted gene panel. RNA-sequencing identified 4047 differentially expressed autosomal genes in pSS B cells. Upregulated expression of type I and type II interferon (IFN)-induced genes was observed, establishing an IFN signature in pSS B cells. Among the top upregulated and validated genes were CX3CR1, encoding the fractalkine receptor involved in regulation of B-cell malignancies, CCL5/RANTES and CCR1. Increased expression of several members of the TNF superfamily was also identified; TNFSF4/Ox40L, TNFSF10/TRAIL, TNFSF13B/BAFF, TNFRSF17/BCMA as well as S100A8 and -A9/calprotectin, TLR7, STAT1 and STAT2. Among genes with downregulated expression in pSS B cells were SOCS1 and SOCS3, CD70 and TNFAIP3/A20. We conclude that B cells from patients with anti-SSA antibody-positive pSS display immune activation with upregulated expression of chemokines, chemokine receptors and a prominent type I and type II IFN signature, while suppressors of cytokine signalling are downregulated. This adds insight into the autoimmune process and suggests potential targets for future functional studies.

  • 32.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Omdal, Roald
    Norheim, Katrine Braekke
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-Wide Analysis of DNA Methylation Profiles in Multiple Tissues in Primary Sjogren's Syndrome2015In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 81, no 5, p. 412-412Article in journal (Other academic)
  • 33. Jonsen, Andreas
    et al.
    Nilsson, Sara C
    Ahlqvist, Emma
    Svenungsson, Elisabet
    Gunnarsson, Iva
    Eriksson, Karin G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bengtsson, Anders
    Zickert, Agneta
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Truedsson, Lennart
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sturfelt, Gunnar
    Blom, Anna M
    Mutations in genes encoding complement inhibitors CD46 and CFH affect the age at nephritis onset in patients with systemic lupus erythematosus2011In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, p. R206-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Inherited deficiencies of several complement components strongly predispose to systemic lupus erythematosus (SLE) while deficiencies of complement inhibitors are found in kidney diseases such as atypical hemolytic uremic syndrome (aHUS).

    METHODS:

    The exons of complement inhibitor genes: CD46 and CFH (factor H) were fully sequenced using Sanger method in SLE patients with nephritis originating from two cohorts from southern and mid Sweden (n = 196). All identified mutations and polymorphisms were then analyzed in SLE patients without nephritis (n = 326) and healthy controls (n = 523).

    RESULTS:

    We found non-synonymous, heterozygous mutations in CFH in 6.1% patients with nephritis in comparison to 4.0% and 5.4% in patients without nephritis and controls, respectively. No associations of SLE or nephritis with common variants in CFH (V62I/Y402H/E936D) were found. Furthermore, we found two non-synonymous heterozygous mutations in CD46 in SLE patients but not in controls. The A353V polymorphism, known to affect function of CD46, was found in 6.6% of nephritis patients vs 4.9% and 6.1% of the non-nephritis SLE patients and controls. The presence of mutations in CD46 and CFH did not predispose to SLE or nephritis but was associated with earlier onset of nephritis. Furthermore, we found weak indications that there is one protective and one risk haplotype predisposing to nephritis composed of several polymorphisms in non-coding regions of CD46, which were previously implicated in aHUS.

    CONCLUSION:

    SLE nephritis is not associated with frequent mutations in CFH and CD46 as found in aHUS but these may be modifying factors causing earlier onset of nephritis.

  • 34.
    Khanam, S.
    et al.
    Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Joachims, M. L.
    Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Means, N.
    Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA;Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA.
    Omdal, R.
    7Stavanger Univ Hosp, Stavanger, Norway.
    Wahren-Herlenius, M.
    Karolinska Inst, Solna, Sweden.
    Alevizos, I.
    Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
    Witte, T.
    Hannover Med Sch, Hannover, Germany.
    Jonsson, R.
    Haukeland Hosp, Bergen, Norway;Univ Bergen, Bergen, Norway.
    Rischmueller, M.
    Univ Adelaide, Adelaide, SA, Australia.
    Rhodus, N. L.
    Univ Minnesota, Minneapolis, MN 55455 USA.
    Montgomery, C.
    Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Ng, W. -F
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Adrianto, I.
    Henry Ford Hlth Syst, Detroit, MI USA.
    Sivils, K.
    Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA;Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA;Henry Ford Hlth Syst, Detroit, MI USA.
    Lessard, C.
    Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA;Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA;Henry Ford Hlth Syst, Detroit, MI USA.
    Functional characterization of the sjögren’s syndrome-associated locus DDX6-CXCR52018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, p. 1267-1267Article in journal (Other academic)
  • 35.
    Khanam, Sharmily
    et al.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Joachims, Michelle L.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Means, Nicholas
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
    Adrianto, Indra
    Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA.
    Rasmussen, Astrid
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Bowman, Simon J.
    Univ Hosp Birmingham, Rheumatol Dept, Birmingham, W Midlands, England.
    Lewis, David M.
    Univ Oklahoma, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA.
    Radfar, Lida
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA;Univ Oklahoma, Coll Dent, Oral Diag & Radiol Dept, Oklahoma City, OK USA.
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
    Wahren-Herleniuss, Marie
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Alevizos, Ilias
    Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA.
    Witte, Torsten
    Hannover Nted Sch, Dept Clin Immunol & Rheumatol, Hannover, Germany.
    Jonsson, Roland
    Haukeland Hosp, Dept Rheumatol, Bergen, Norway;Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.
    Rischmueller, Maureen
    Queen Elizabeth Hosp, Dept Rheumatol, Adelaide, SA, Australia;Univ Adelaide, Discipline Med, Adelaide, SA, Australia.
    Gaffney, Patrick M.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    James, Judith A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Theander, Elke
    Lund Univ, Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden.
    Rhodus, Nelson L.
    Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA.
    Segal, Barbara M.
    Univ Minnesota, Sch Med, Div Rheumatol, Minneapolis, MN 55455 USA.
    Scofield, R. Hal
    Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA;Dept Vet Affairs Med Ctr, Oklahoma City, OK USA.
    Montgomery, Courtney G.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Mariette, Xavier
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, INSERM,U1012, Paris, France.
    Ng, Wan-Fai
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sivils, Kathy L.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
    Lessard, Christopher J.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Progam, 825 NE 13th St, Oklahoma City, OK 73104 USA;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
    Functional characterization of the Sjögren's syndrome-associated locus DDX6-CXCR52018In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, no 3, p. S286-S287Article in journal (Other academic)
  • 36.
    Kiani, Rezvan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Vasaitis, Lilian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Svanberg, Anncarin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Fatigue correlates with mental health and quality of life in primary Sjogren's syndrome2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no S127, p. 37-38Article in journal (Other academic)
  • 37.
    Knight, A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eva, Kumlien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fatal outcome of tick-borne encephalitis in two patients with rheumatic disease treated with rituximab.2017In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, no 5, p. 855-856Article in journal (Refereed)
  • 38. Kottyan, Leah C
    et al.
    Zoller, Erin E
    Bene, Jessica
    Lu, Xiaoming
    Kelly, Jennifer A
    Rupert, Andrew M
    Lessard, Christopher J
    Vaughn, Samuel E
    Marion, Miranda
    Weirauch, Matthew T
    Namjou, Bahram
    Adler, Adam
    Rasmussen, Astrid
    Glenn, Stuart
    Montgomery, Courtney G
    Hirschfield, Gideon M
    Xie, Gang
    Coltescu, Catalina
    Amos, Chris
    Li, He
    Ice, John A
    Nath, Swapan K
    Mariette, Xavier
    Bowman, Simon
    Rischmueller, Maureen
    Lester, Sue
    Brun, Johan G
    Gøransson, Lasse G
    Harboe, Erna
    Omdal, Roald
    Cunninghame-Graham, Deborah S
    Vyse, Tim
    Miceli-Richard, Corinne
    Brennan, Michael T
    Lessard, James A
    Wahren-Herlenius, Marie
    Kvarnström, Marika
    Illei, Gabor G
    Witte, Torsten
    Jonsson, Roland
    Eriksson, Per
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Ng, Wan-Fai
    Anaya, Juan-Manuel
    Rhodus, Nelson L
    Segal, Barbara M
    Merrill, Joan T
    James, Judith A
    Guthridge, Joel M
    Hal Scofield, R
    Alarcon-Riquelme, Marta
    Bae, Sang-Cheol
    Boackle, Susan A
    Criswell, Lindsey A
    Gilkeson, Gary
    Kamen, Diane L
    Jacob, Chaim O
    Kimberly, Robert
    Brown, Elizabeth
    Edberg, Jeffrey
    Alarcón, Graciela S
    Reveille, John D
    Vilá, Luis M
    Petri, Michelle
    Ramsey-Goldman, Rosalind
    Freedman, Barry I
    Niewold, Timothy
    Stevens, Anne M
    Tsao, Betty P
    Ying, Jun
    Mayes, Maureen D
    Gorlova, Olga Y
    Wakeland, Ward
    Radstake, Timothy
    Martin, Ezequiel
    Martin, Javier
    Siminovitch, Katherine
    Moser Sivils, Kathy L
    Gaffney, Patrick M
    Langefeld, Carl D
    Harley, John B
    Kaufman, Kenneth M
    The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share2015In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, no 2, p. 582-596Article in journal (Refereed)
    Abstract [en]

    Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.

  • 39.
    Landegren, Nils
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Pourmousa Lindberg, Mina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Skov, Jakob
    Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Hallgren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Eriksson, Daniel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Lisberg Toft-Bertelsen, Trine
    Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark.
    MacAulay, Nanna
    Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark.
    Hagforsen, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Räisänen-Sokolowski, Anne
    Helsinki Univ Hosp, Dept Pathol, Helsinki, Finland.; Univ Helsinki, Helsinki, Finland.
    Saha, Heikki
    Tampere Univ Hosp, Sch Med, Dept Med, Tampere, Finland.
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Ohlsson, Sophie
    Lund Univ, Dept Nephrol, Lund, Sweden.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Husebye, Eystein S
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.; Univ Bergen, Dept Clin Sci, Bergen, Norway.; Haukeland Hosp, Dept Med, Bergen, Norway.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Anderson, Mark S
    Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
    Perheentupa, Jaakko
    Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Fenton, Robert A
    Aarhus Univ, Dept Biomed, Interact Prot Epithelial Transport Ctr, Aarhus, Denmark.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis.2016In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, no 10, p. 3220-3228Article in journal (Refereed)
    Abstract [en]

    Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.

  • 40.
    Leonard, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Svenungsson, E.
    Sandling, J. K.
    Berggren, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Jonsen, A.
    Bengtsson, C.
    Wang, C.
    Jensen-Urstad, K.
    Granstam, Sven-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bengtsson, A. A.
    Gustafsson, J. T.
    Gunnarsson, I.
    Rantapaa-Dahlqvist, S.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvanen, A-C
    Ronnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Coronary Heart Disease in Systemic Lupus Erythematosus is Associated with Interferon Regulatory Factor 8 Gene Variants2013In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, no S3, p. 270-270Article in journal (Other academic)
  • 41.
    Leonard, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Svenungsson, Elisabet
    Sandling, Johanna K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Berggren, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Jönsen, Andreas
    Bengtsson, Christine
    Wang, Chuan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jensen-Urstad, Kerstin
    Granstam, Sven-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bengtsson, Anders A
    Gustafsson, Johanna T
    Gunnarsson, Iva
    Rantapää-Dahlqvist, Solbritt
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Coronary heart disease in systemic lupus erythematosus is associated with interferon regulatory factor-8 gene variants2013In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 6, no 3, p. 255-263Article in journal (Refereed)
    Abstract [en]

    Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r(2)=0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1-6.3), P value 1.9×10(-6). The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques (P<0.001) and increased intima-media thickness (P=0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions- There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus.

  • 42. Lessard, C. J.
    et al.
    Li, H.
    Ice, J. A.
    Adrianto, I.
    Jonsson, R.
    Illei, G. G.
    Rischmueller, M.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Mariette, X.
    Miceli-Richard, C.
    Herlenius, M. Wahren
    Witte, T.
    Brennan, M.
    Omdal, R.
    Gaffney, P. M.
    Lessard, J. A.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Ng, W. -F
    Rhodus, N.
    Segal, B.
    Scofield, R. H.
    James, J. A.
    Anaya, J. -M
    Montgomery, C. G.
    Harley, J. B.
    Sivils, K. Moser
    Identification of Multiple Sjogren'S Syndrome Susceptibility Loci2013In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, no S3, p. 54-55Article in journal (Other academic)
  • 43.
    Lessard, C.
    et al.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA..
    Li, H.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA..
    Ice, J. A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Adrianto, I.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Rasmussen, A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Lewis, D. M.
    Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA..
    Radfar, L.
    Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA..
    Stone, D. U.
    Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA..
    Montgomery, C. G.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Rhodus, N. L.
    Univ Minnesota, Sch Dent, Minneapolis, MN 55455 USA..
    Scofield, R. H.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA..
    Farris, A. D.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Omdal, R.
    Stavanger Univ Hosp, Stavanger, Norway..
    Wahren-Herlenius, M.
    Karolinska Inst, Stockholm, Sweden..
    Alevizos, I.
    Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA..
    Witte, T.
    Hannover Med Sch, Hannover, Germany..
    Jonsson, R.
    Haukeland Hosp, Bergen, Norway.;Univ Bergen, Bergen, Norway..
    Rischmueller, M.
    Queen Elizabeth Hosp, Adelaide, SA, Australia.;Univ Adelaide, Adelaide, SA, Australia..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Mariette, X.
    Hop Univ Paris Sud, Paris, France..
    Ng, W. -F
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sivils, K. L.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA..
    Identification of Sjögren's Syndrome Risk Loci near TNFAIP3 and PRDM12016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. 664-664Article in journal (Other academic)
  • 44. Lessard, Christopher J.
    et al.
    Li, He
    Adrianto, Indra
    Ice, John A.
    Dozmorov, Mikhail G.
    Jonsson, Roland
    Rischmueller, Maureen
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Mariette, Xavier
    Miceli-Richard, Corinne
    Wahren-Herlenius, Marie
    Witte, Torsten
    Brennan, Michael T.
    Omdal, Roald
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Gaffney, Patrick M.
    Ng, Wan-Fai
    Rhodus, Nelson L.
    Segal, Barbara M.
    Wren, Jonathan D.
    Scofield, R. Hal
    Anaya, Juan-Manuel
    Harley, John B.
    Montgomery, Courtney G.
    Sivils, Kathy L.
    Complex Functional Effects Within The HLA Contribute To Sjogren's Syndrome Pathogenesis and May Influence Both Transcriptional Regulation and Peptide Binding2013In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, no Suppl. 10, p. S1184-S1185Article in journal (Other academic)
  • 45. Lessard, Christopher J
    et al.
    Li, He
    Adrianto, Indra
    Ice, John A
    Rasmussen, Astrid
    Grundahl, Kiely M
    Kelly, Jennifer A
    Dozmorov, Mikhail G
    Miceli-Richard, Corinne
    Bowman, Simon
    Lester, Sue
    Eriksson, Per
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Brun, Johan G
    Gøransson, Lasse G
    Harboe, Erna
    Guthridge, Joel M
    Kaufman, Kenneth M
    Kvarnström, Marika
    Jazebi, Helmi
    Cunninghame Graham, Deborah S
    Grandits, Martha E
    Nazmul-Hossain, Abu N M
    Patel, Ketan
    Adler, Adam J
    Maier-Moore, Jacen S
    Farris, A Darise
    Brennan, Michael T
    Lessard, James A
    Chodosh, James
    Gopalakrishnan, Rajaram
    Hefner, Kimberly S
    Houston, Glen D
    Huang, Andrew J W
    Hughes, Pamela J
    Lewis, David M
    Radfar, Lida
    Rohrer, Michael D
    Stone, Donald U
    Wren, Jonathan D
    Vyse, Timothy J
    Gaffney, Patrick M
    James, Judith A
    Omdal, Roald
    Wahren-Herlenius, Marie
    Illei, Gabor G
    Witte, Torsten
    Jonsson, Roland
    Rischmueller, Maureen
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ng, Wan-Fai
    Mariette, Xavier
    Anaya, Juan-Manuel
    Rhodus, Nelson L
    Segal, Barbara M
    Scofield, R Hal
    Montgomery, Courtney G
    Harley, John B
    Sivils, Kathy L
    Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1284-1292Article in journal (Refereed)
    Abstract [en]

    Sjögren's syndrome is a common autoimmune disease (affecting ~0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10−114), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10−19), STAT4 (Pmeta = 6.80 × 10−15), IL12A (Pmeta = 1.17 × 10−10), FAM167A-BLK (Pmeta = 4.97 × 10−10), DDX6-CXCR5 (Pmeta = 1.10 × 10−8) and TNIP1 (Pmeta = 3.30 × 10−8). We also observed suggestive associations (Pmeta < 5 × 10−5) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögren's syndrome.

  • 46.
    Lessard, Christopher J.
    et al.
    Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Li, He
    Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Ice, John
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Adrianto, Indra
    Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA..
    Rasmussen, Astrid
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Grundahl, Kiely
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Kelly, Jennifer A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Miceli, Corinne
    Bowman, Simon
    Univ Hosp Birmingham, Dept Rheumatol, Birmingham, W Midlands, England..
    Lester, Susan
    Queen Elizabeth Hosp, Adelaide, SA, Australia..
    Brun, Johan G.
    Univ Bergen, Inst Internal Med, Bergen, Norway.;Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway..
    Goransson, Lasse G.
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Harboe, Erna
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Guthridge, Joel M.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Kaufman, Kenneth M.
    US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.;Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA..
    Eriksson, Per
    Linkoping Univ, Rheumatol AIR, Dept Clin & Expt Med, Linkoping, Sweden..
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kvarnstrom, Marika
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Cunninghame-Graham, Deborah S.
    Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England..
    Farris, A. Darise
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Brennan, Michael T.
    Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA..
    Chodosh, James
    Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalmol, Boston, MA USA..
    Gopalakrishnan, Raj
    Univ Minnesota, Div Oral Pathol, Diagnost & Biol Sci, Minneapolis, MN USA..
    Huang, Andrew J. W.
    Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA..
    Hughes, Pamela
    Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA..
    Lewis, David M.
    Univ Oklahoma, Hlth Sci Ctr, Dept Oral & Maxillofacial Pathol, Coll Dent, Oklahoma City, OK USA..
    Radfar, Lida
    Univ Oklahoma, Hlth Sci Ctr, Oral Diag & Radiol Dept, Coll Dent, Oklahoma City, OK USA..
    Rohrer, Michael D.
    Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA..
    Stone, Donald U.
    Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA..
    Vyse, Timothy J.
    Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England..
    Gaffney, Patrick M.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    James, Judith A.
    Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA..
    Harley, John B.
    US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.;Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA..
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Wahren-Herlenius, Marie
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Illei, Gabor G.
    Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA..
    Witte, Torsten
    Hannover Med Sch, Hannover, Germany..
    Jonsson, Roland
    Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway.;Univ Bergen, Gade Inst, Broegelmann Res Lab, Bergen, Norway..
    Rischmueller, Maureen
    Univ Adelaide, Adelaide, SA, Australia.;Queen Elizabeth Hosp, Dept Rheumatol, Adelaide, SA, Australia..
    Ronnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mariette, Xavier
    Univ Paris 11, Hop Univ Paris Sud, AP HP, Paris, France..
    Anaya, Juan-Manuel
    Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota, Colombia..
    Ng, Wan-Fai
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England..
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Dept Med Sci, Rheumatol, Uppsala, Sweden.;Uppsala Univ, Sci Life Lab, Uppsala, Sweden..
    Montgomery, Courtney G.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Rhodus, Nelson L.
    Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA..
    Segal, Barbara M.
    Univ Minnesota, Sch Med, Div Rheumatol, Minneapolis, MN 55455 USA..
    Scofield, R. Hal
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.;US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA..
    Sivils, Kathy L.
    Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Identification of Novel Sjogren's Syndrome Risk Loci in the Regions of TNFAIP3 and PRDM12015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl. 10, article id 1052Article in journal (Other academic)
  • 47.
    Li, He
    et al.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA..
    Reksten, Tove Ragna
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway..
    Ice, John A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Kelly, Jennifer A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Adrianto, Indra
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Rasmussen, Astrid
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Wang, Shaofeng
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    He, Bo
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA..
    Grundahl, Kiely M.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Glenn, Stuart B.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Miceli-Richard, Corinne
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, INSERM,U1012, Le Kremlin Bicetre, France..
    Bowman, Simon
    Univ Hosp Birmingham, Rheumatol Dept, Birmingham, W Midlands, England..
    Lester, Sue
    Queen Elizabeth Hosp, Adelaide, SA, Australia..
    Eriksson, Per
    Linkoping Univ, Dept Rheumatol Clin & Expt Med, Linkoping, Sweden..
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Brun, Johan G.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Haukeland Hosp, Dept Rheumatol, Bergen, Norway..
    Goransson, Lasse G.
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Harboe, Erna
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Guthridge, Joel M.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Kaufman, Kenneth M.
    Cincinnati Childrens Hosp Med Ctr, Div Rheurnatol, Cincinnati, OH 45229 USA.;US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA..
    Kvarnstrom, Marika
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Graham, Deborah S. Cunninghame
    Kings Coll London, Dept Med & Mol Genet, London, England..
    Patel, Ketan
    Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA.;North Mem Med Ctr, Dept Oral & Maxillofacial Surg, Robbinsdale, MN USA..
    Adler, Adam J.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Farris, A. Darise
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA..
    Brennan, Michael T.
    Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA..
    Chodosh, James
    Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA..
    Gopalakrishnan, Rajaram
    Univ Minnesota, Sch Dent, Dept Diagnost & Biol Sci, Div Oral Pathol, Minneapolis, MN 55455 USA..
    Weisman, Michael H.
    Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA..
    Venuturupalli, Swamy
    Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA..
    Wallace, Daniel J.
    Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA..
    Hefner, Kimberly S.
    Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA.;Hefner Eye Care & Opt Ctr, Oklahoma City, OK USA..
    Houston, Glen D.
    Univ Oklahoma, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA.;Heartland Pathol Consultants, Edmond, OK USA..
    Huang, Andrew J. W.
    Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA..
    Hughes, Pamela J.
    Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA..
    Lewis, David M.
    Univ Oklahoma, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA..
    Radfar, Lida
    Univ Oklahoma, Coll Dent, Oral Diagnosis & Radiol Dept, Oklahoma City, OK USA..
    Vista, Evan S.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Santo Tomas Hosp, Manila, Philippines..
    Edgar, Contessa E.
    Oklahoma Baptist Univ, Biol Dept, Oklahoma City, OK USA..
    Rohrer, Michael D.
    Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA..
    Stone, Donald U.
    Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA..
    Vyse, Timothy J.
    Kings Coll London, Dept Med & Mol Genet, London, England..
    Harley, John B.
    Cincinnati Childrens Hosp Med Ctr, Div Rheurnatol, Cincinnati, OH 45229 USA.;US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA..
    Gaffney, Patrick M.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    James, Judith A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA..
    Turner, Sean
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Alevizos, Ilias
    Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA..
    Anaya, Juan-Manuel
    Univ Rosario, Cente Autoimmune Dis Res, Bogota, Colombia..
    Rhodus, Nelson L.
    Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA..
    Segal, Barbara M.
    Univ Minnesota, Sch Med, Div Rheumatol, Minneapolis, MN 55455 USA..
    Montgomery, Courtney G.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Scofield, R. Hal
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.;US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA..
    Kovats, Susan
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Mariette, Xavier
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, INSERM,U1012, Le Kremlin Bicetre, France..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Witte, Torsten
    Hannover Med Sch, Clin Immunol & Rheumatol, Hannover, Germany..
    Rischmueller, Maureen
    Queen Elizabeth Hosp, Adelaide, SA, Australia.;Univ Adelaide, Adelaide, SA, Australia..
    Wahren-Herlenius, Marie
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Jonsson, Roland
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.;Haukeland Hosp, Dept Rheumatol, Bergen, Norway..
    Ng, Wan-Fai
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.;Newcastle Univ, NIHR Newcastle Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England..
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lessard, Christopher J.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA..
    Sivils, Kathy L.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA..
    Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 6, article id e1006820Article in journal (Refereed)
    Abstract [en]

    Sjogren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 x 10(-14)). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (P-meta = 2.59 x 10(-9); odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.

  • 48.
    Linga-Reddy, M. V. Prasad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gunnarsson, I
    Svenungsson, E
    Sturfelt, G
    Jönsen, A
    Truedsson, L
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alarcón-Riquelme, Marta E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    A polymorphic variant in the MHC2TA gene is not associated with systemic lupus erythematosus2007In: Tissue Antigens, ISSN 0001-2815, E-ISSN 1399-0039, Vol. 70, no 5, p. 412-414Article in journal (Refereed)
    Abstract [en]

    Single-nucleotide polymorphisms (SNPs) in the major histocompatibility complex class II transactivator (MHC2TA) gene encoding the class II transactivator have been associated with multiple sclerosis, rheumatoid arthritis, and myocardial infarction in the Swedish population. We used a case-control approach to investigate the prevalence of a relevant variant in Swedish systemic lupus erythematosus (SLE) cohorts to determine whether SLE shares the same MHC2TA susceptibility allele as the other diseases. No differences were observed between cases and control subjects at either the allele or genotype levels. Furthermore, no significant correlations were found when comparing different clinical and serological SLE phenotypes. This particular polymorphism rs3087456 of the MHC2TA gene does not appear to influence genetic susceptibility to SLE in the Swedish population. We conclude that our data support neither allelic nor genotype association between the MHC2TA SNP and SLE.

  • 49. Liu, Ke
    et al.
    Kaufman, Kenneth M.
    James, Judith A.
    Jonsson, Roland
    Kurien, Biji T.
    Mariette, Xavier
    Merrill, Joan T.
    Omdal, Roald
    Rischmueller, Maureen
    Vyse, Timothy J.
    Wahren-Herlenius, Marie
    Witte, Torsten
    Lessard, Christopher J.
    Zimmerman, Sarah L.
    Thompson, Susan D.
    Hirschfield, Gideon
    Xie, Gang
    Montgomery, Courtney G.
    Ng, Wan-Fai
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Gaffney, Patrick M.
    Siminovitch, Katherine A.
    Sivils, Kathy L.
    Scofield, R. Hal
    Sex Bias In Autoimmune Diseases: Increased Risk Of 47,XXX In Systemic Lupus Erythematosus (SLE) and Sjogren's Syndrome (SS) Supports The Gene Dose Hypothesis2013In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, no Suppl. 10, p. S379-S379Article in journal (Other academic)
  • 50. Liu, Ke
    et al.
    Kurien, Biji T
    Zimmerman, Sarah L
    Kaufman, Kenneth M
    Taft, Diana H
    Kottyan, Leah C
    Lazaro, Sara
    Weaver, Carrie A
    Ice, John A
    Adler, Adam J
    Chodosh, James
    Radfar, Lida
    Rasmussen, Astrid
    Stone, Donald U
    Lewis, David M
    Li, Shibo
    Koelsch, Kristi A
    Igoe, Ann
    Talsania, Mitali
    Kumar, Jay
    Maier-Moore, Jacen S
    Harris, Valerie M
    Gopalakrishnan, Rajaram
    Jonsson, Roland
    Lessard, James A
    Lu, Xianglan
    Gottenberg, Jacques-Eric
    Anaya, Juan-Manuel
    Cunninghame-Graham, Deborah S
    Huang, Andrew J W
    Brennan, Michael T
    Hughes, Pamela
    Illei, Gabor G
    Miceli-Richard, Corinne
    Keystone, Edward C
    Bykerk, Vivian P
    Hirschfield, Gideon
    Xie, Gang
    Ng, Wan-Fai
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eriksson, Per
    Omdal, Roald
    Rhodus, Nelson L
    Rischmueller, Maureen
    Rohrer, Michael
    Segal, Barbara M
    Vyse, Timothy J
    Wahren-Herlenius, Marie
    Witte, Torsten
    Pons-Estel, Bernardo
    Alarcon-Riquelme, Marta E
    Guthridge, Joel M
    James, Judith A
    Lessard, Christopher J
    Kelly, Jennifer A
    Thompson, Susan D
    Gaffney, Patrick M
    Montgomery, Courtney G
    Edberg, Jeffrey C
    Kimberly, Robert P
    Alarcón, Graciela S
    Langefeld, Carl L
    Gilkeson, Gary S
    Kamen, Diane L
    Tsao, Betty P
    McCune, W Joseph
    Salmon, Jane E
    Merrill, Joan T
    Weisman, Michael H
    Wallace, Daniel J
    Utset, Tammy O
    Bottinger, Erwin P
    Amos, Christopher I
    Siminovitch, Katherine A
    Mariette, Xavier
    Sivils, Kathy L
    Harley, John B
    Scofield, R Hal
    X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome2016In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 68, no 5, p. 1290-1300Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    More than 80% of autoimmune disease is female dominant, but the mechanism for this female bias is poorly understood. We suspected an X chromosome dose effect and hypothesized that trisomy X (47,XXX, 1 in ∼1,000 live female births) would be increased in female predominant diseases (e.g. systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis [PBC] and rheumatoid arthritis [RA]) compared to diseases without female predominance (sarcoidosis) and controls.

    METHODS:

    We identified 47,XXX subjects using aggregate data from single nucleotide polymorphism (SNP) arrays and confirmed, when possible, by fluorescent in situ hybridization (FISH) or quantitative polymerase chain reaction (q-PCR).

    RESULTS:

    We found 47,XXX in seven of 2,826 SLE and three of 1,033 SS female patients, but only in two of the 7,074 female controls (p=0.003, OR=8.78, 95% CI: 1.67-86.79 and p=0.02, OR=10.29, 95% CI: 1.18-123.47; respectively). One 47,XXX subject was present for ∼404 SLE women and ∼344 SS women. 47,XXX was present in excess among SLE and SS subjects.

    CONCLUSION:

    The estimated prevalence of SLE and SS in women with 47,XXX was respectively ∼2.5 and ∼2.9 times higher than in 46,XX women and ∼25 and ∼41 times higher than in 46,XY men. No statistically significant increase of 47,XXX was observed in other female-biased diseases (PBC or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. This article is protected by copyright. All rights reserved.

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